2016 International Symposium on Chemical Biology of the
... (rapalogues), which act as allosteric inhibitors. More recently, ATP-competitive inhibitors that directly target the active site of the mTOR kinase domain were developed. Both types of drugs may easily lose their potency by single point mutations in the respective binding domains. Based on the recen ...
... (rapalogues), which act as allosteric inhibitors. More recently, ATP-competitive inhibitors that directly target the active site of the mTOR kinase domain were developed. Both types of drugs may easily lose their potency by single point mutations in the respective binding domains. Based on the recen ...
PPT Version - OMICS International
... pyrazole based Aurora kinase inhibitor PHA-739358. However, the compounds may not effectively dock to ER-α ligand binding site as PHA-739358. The compounds bound out of ER-α ligand binding region as shown in Figure 8. It was proposed that addition of acyl thiourea group changed the binding character ...
... pyrazole based Aurora kinase inhibitor PHA-739358. However, the compounds may not effectively dock to ER-α ligand binding site as PHA-739358. The compounds bound out of ER-α ligand binding region as shown in Figure 8. It was proposed that addition of acyl thiourea group changed the binding character ...
2015 department of medicine research day
... Rationale: KD019 was originally developed for a solid tumor indication, and is currently being investigated as a cancer treatment. In non-clinical studies, KD019 selectively inhibited key kinases and validated targets in animal models of polycystic kidney disease (PKD). In addition, it has shown eit ...
... Rationale: KD019 was originally developed for a solid tumor indication, and is currently being investigated as a cancer treatment. In non-clinical studies, KD019 selectively inhibited key kinases and validated targets in animal models of polycystic kidney disease (PKD). In addition, it has shown eit ...
Max ARM (Anabolic Recovery Matrix) from Max Muscle Sports
... enzymes Akt/mTOR (rapamycin), a protein kinase and the sequential stimulation of p70 ribosomal S6 kinase (p70 S6K) through enhanced translation of specific mRNAs. The Akt/mTOR pathway in muscle is upregulated during the hypertrophy (increase in muscle size) phase.† An exciting area in the molecular ...
... enzymes Akt/mTOR (rapamycin), a protein kinase and the sequential stimulation of p70 ribosomal S6 kinase (p70 S6K) through enhanced translation of specific mRNAs. The Akt/mTOR pathway in muscle is upregulated during the hypertrophy (increase in muscle size) phase.† An exciting area in the molecular ...
AMPK and mTOR: Antagonist ATP Sensors
... specifically of leucine availability. Research has shown that regulation of mTOR by ATP and amino acids act independently through separate mechanisms (Dennis et al., 2001). Leucine is the key regulator of the mTOR-signaling pathway (Anthony et al. 2001 & Lynch et al. 2002). According to Laymen (2003 ...
... specifically of leucine availability. Research has shown that regulation of mTOR by ATP and amino acids act independently through separate mechanisms (Dennis et al., 2001). Leucine is the key regulator of the mTOR-signaling pathway (Anthony et al. 2001 & Lynch et al. 2002). According to Laymen (2003 ...
Akt Inhibitors MK-2206 and Nelfinavir Overcome mTOR Inhibitor
... properties, yielded synergistic inhibition of cell viability in combination with rapamycin in DLBCL cell lines, and potently inhibited phosphorylation of Akt and downstream targets of activated mTOR. Conclusions: GEP identifies DLBCL subsets resistant to mTOR inhibitor therapy. Combined targeting of ...
... properties, yielded synergistic inhibition of cell viability in combination with rapamycin in DLBCL cell lines, and potently inhibited phosphorylation of Akt and downstream targets of activated mTOR. Conclusions: GEP identifies DLBCL subsets resistant to mTOR inhibitor therapy. Combined targeting of ...
Metabolism Drug Resistance
... signaling occur frequently in epithelial cancers. However, the coordination of these two processes by PI3K is not fully understood. Hu and colleagues found that PI3K inhibitors resulted in decreased glycolytic capacity in mammary epithelial cells, whereas AKT and mTOR inhibitors did not have this ef ...
... signaling occur frequently in epithelial cancers. However, the coordination of these two processes by PI3K is not fully understood. Hu and colleagues found that PI3K inhibitors resulted in decreased glycolytic capacity in mammary epithelial cells, whereas AKT and mTOR inhibitors did not have this ef ...
fact sheet
... naturally occurring lipids with variations on chain length, unsaturation level, chemical radicals and salts. Several compounds have been synthesized and evaluated as anticancer drugs. 2 drug candidates have been selected for development. The lipid analogues → influence the activity of proteins which ...
... naturally occurring lipids with variations on chain length, unsaturation level, chemical radicals and salts. Several compounds have been synthesized and evaluated as anticancer drugs. 2 drug candidates have been selected for development. The lipid analogues → influence the activity of proteins which ...
Protein Kinase Inhibitors in Research and Medicine, Vol 548. Methods... Enzymology Brochure
... Brochure More information from http://www.researchandmarkets.com/reports/2496373/ ...
... Brochure More information from http://www.researchandmarkets.com/reports/2496373/ ...
New Options for patients with imatinib
... Signalling pathways and targets involved in SCCHN and their potential inhibitors ...
... Signalling pathways and targets involved in SCCHN and their potential inhibitors ...
Adenovirus Overrides Cellular Checkpoints for Protein Translation
... which plays an important role in regulating protein translation in response to nutrient and growth factor signals. mTOR is a kinase that was first isolated as the target of the macrolide drug rapamycin,7 which has potent inhibitory effects on cell growth and replication. mTOR activation induces the ...
... which plays an important role in regulating protein translation in response to nutrient and growth factor signals. mTOR is a kinase that was first isolated as the target of the macrolide drug rapamycin,7 which has potent inhibitory effects on cell growth and replication. mTOR activation induces the ...
mTORC1 regulates the efficiency and cellular capacity for protein
... rapamycin, showing that the effects are mediated through mTORC1. The finding that eEF2K is phosphorylated (on Ser366 ) and inactivated by S6K [11] seemed to provide the link between mTORC1 and the control of eEF2K (Figure 2). It also provided a connection to the oncogenic Ras/Raf/MEK [MAPK (mitogen- ...
... rapamycin, showing that the effects are mediated through mTORC1. The finding that eEF2K is phosphorylated (on Ser366 ) and inactivated by S6K [11] seemed to provide the link between mTORC1 and the control of eEF2K (Figure 2). It also provided a connection to the oncogenic Ras/Raf/MEK [MAPK (mitogen- ...
Nature Cell Biol. 6
... 200 nM). The addition of insulin induced the formation of lamellipodia and membrane ruffles, which was also insensitive to pre-treatment with rapamycin (see Supplementary Information, Fig. S1). The addition of lysophosphatidic acid (LPA) also led to rapamycin-insensitive formation of stress fibres. ...
... 200 nM). The addition of insulin induced the formation of lamellipodia and membrane ruffles, which was also insensitive to pre-treatment with rapamycin (see Supplementary Information, Fig. S1). The addition of lysophosphatidic acid (LPA) also led to rapamycin-insensitive formation of stress fibres. ...
Alsace BioValley
... using FRESH tumours xenografted and maintained in nude mice (32 kidney, 6 bladder and 5 prostate cancer models). They can assess the anti-cancer efficiency of drug candidates with the possibility to identify predictive biomarkers associated to the treatment. More information at www.urolead.com. ...
... using FRESH tumours xenografted and maintained in nude mice (32 kidney, 6 bladder and 5 prostate cancer models). They can assess the anti-cancer efficiency of drug candidates with the possibility to identify predictive biomarkers associated to the treatment. More information at www.urolead.com. ...
MICROBIOTIX, INC
... Health/NIAID. The SBIR Phase I grant entitled, “Structure-Based Design of Sortase Inhibitors for AntiInfective Therapy” provides two years of support to discover, develop, and synthesize small molecule inhibitors of Sortase A for anti-infective therapy, e.g. for the treatment of Gram-positive bacter ...
... Health/NIAID. The SBIR Phase I grant entitled, “Structure-Based Design of Sortase Inhibitors for AntiInfective Therapy” provides two years of support to discover, develop, and synthesize small molecule inhibitors of Sortase A for anti-infective therapy, e.g. for the treatment of Gram-positive bacter ...
Discovery of potent inhibitors of the epigenetic cancer target PRMT4
... [5] Kessenbrock K, Plaks V, Werb Z. Matrix metalloproteinases: regulators of the tumormicroenvironment. Cell. 2010;141(1):52-67. [6] Majumder S, Liu Y, Ford OH, 3rd, Mohler JL, Whang YE. Involvement of argininemethyltransferase CARM1 in androgen receptor function and prostate cancer cell viability. ...
... [5] Kessenbrock K, Plaks V, Werb Z. Matrix metalloproteinases: regulators of the tumormicroenvironment. Cell. 2010;141(1):52-67. [6] Majumder S, Liu Y, Ford OH, 3rd, Mohler JL, Whang YE. Involvement of argininemethyltransferase CARM1 in androgen receptor function and prostate cancer cell viability. ...
New anticancer compounds could boost effectiveness of standard
... guinea pig model without causing toxicity. Lixte’s product pipeline also includes new agents in the LB-300 and LB-400 series. These compounds, which are at the discovery and proofof-concept stages, inhibit signaling pathways involved in cell division and other important cellular processes necessary ...
... guinea pig model without causing toxicity. Lixte’s product pipeline also includes new agents in the LB-300 and LB-400 series. These compounds, which are at the discovery and proofof-concept stages, inhibit signaling pathways involved in cell division and other important cellular processes necessary ...
View Full PDF - Biochemical Society Transactions
... for subsequent analyses. Importantly, one of these soil samples contained the bacterium Streptomyces hygroscopicus that was found to produce a secondary metabolite, now known as rapamycin, with potent antifungal activity [1,2]. Not long after its initial characterization as an antifungal agent, rapa ...
... for subsequent analyses. Importantly, one of these soil samples contained the bacterium Streptomyces hygroscopicus that was found to produce a secondary metabolite, now known as rapamycin, with potent antifungal activity [1,2]. Not long after its initial characterization as an antifungal agent, rapa ...
Chemical Biology I (DM)
... 3. Optimize your initial lead compound by making analogs (SAR) and by using any additional biochemical/structural information. In parallel, screen optimized analogs against other targets (selectivity) ...
... 3. Optimize your initial lead compound by making analogs (SAR) and by using any additional biochemical/structural information. In parallel, screen optimized analogs against other targets (selectivity) ...
Regulation of protein synthesis by insulin
... by eIF2B (Figure 1). This GDP/GTP exchange process is a key regulatory step for translation initiation under many conditions: for example, it is inhibited by phosphorylation of eIF2’s α-subunit by any one of four mammalian eIF2 kinases, which are activated under specific stress conditions [3]. The r ...
... by eIF2B (Figure 1). This GDP/GTP exchange process is a key regulatory step for translation initiation under many conditions: for example, it is inhibited by phosphorylation of eIF2’s α-subunit by any one of four mammalian eIF2 kinases, which are activated under specific stress conditions [3]. The r ...
The TOR signalling network from yeast to man
... While it is not known how, or even if, y/mTORC2 is regulated, y/mTORC1 is—via yet poorly understood mechanisms—regulated by nutrient quality and/or abundance. In addition, mTORC1 activity is influenced by growth factors, energy, and cellular stress, and recent studies in fly and mammalian tissue cul ...
... While it is not known how, or even if, y/mTORC2 is regulated, y/mTORC1 is—via yet poorly understood mechanisms—regulated by nutrient quality and/or abundance. In addition, mTORC1 activity is influenced by growth factors, energy, and cellular stress, and recent studies in fly and mammalian tissue cul ...
... • The PI3K/Akt/mTOR pathway is an important signaling pathway for many cellular regulation functions such as cell proliferation, angiogenesis and vascular permeability – Significant therapeutic opportunities for pathway signaling – Agents in development affect different targets • PI3K inhibitors • A ...
p38 MAP Kinase Inhibitor - Lilly Oncology Pipeline USA
... p38 mitogen-activated protein (MAP) kinase is activated in response to inflammatory stimuli (eg, tumor necrosis factor, interleukin-6), growth factors (eg, vascular endothelial growth factor, fibroblast growth factor, insulin-like growth factor), and cellular stress (eg, chemotherapeutic challenge). ...
... p38 mitogen-activated protein (MAP) kinase is activated in response to inflammatory stimuli (eg, tumor necrosis factor, interleukin-6), growth factors (eg, vascular endothelial growth factor, fibroblast growth factor, insulin-like growth factor), and cellular stress (eg, chemotherapeutic challenge). ...